Evolution of benign thyroid nodules under levothyroxine non-suppressive therapy

Background: Non-suppressive or partially suppressive L-T4 treatment demonstrated to be effective in reducing the volume of the nodules. However, studies with long follow-up are lacking and significant controversy exists regarding the efficacy of non-suppressive L-T4 treatment in benign nodular goiter. Aim: The goal of this study was to determine the evolution of thyroid nodules in subjects treated with a non-suppressive levothyroxine (L-T4) dose, compared to untreated subjects. Design and patients: We followed for a period of 1-9 years the thyroid nodule size in 356 female patients in the age range 19-45 at study entry, of which 201 untreated (Group 0) and 165 treated with a non-suppressive L-T4 dose (Group L-T4). Measurements: We determined the volume of thyroid nodules by ultrasonography. Results: The initial mean nodule volume in Group 0 and Group L-T4 was 3.91 ± 6.87 and 4.01 ± 7.35 mL, respectively. Nodule volume increase was inversely correlated to the initial volume. The final volume was slightly higher in untreated than in L-T4 treated subjects (5.37 ± 8.49 and 4.39 ± 6.72 mL). In both groups, the mean of annual fold increase of nodule volume was inversely correlated with the follow-up duration (P <0.0046), indicating a slower growth as time advances. In the subjects treated with L-T4, the mean annual increase of nodule volume was significantly minor compared to untreated subjects. Concomitant nodules in ten multinodular goiters exhibited totally independent evolution, demonstrating that intranodular factors are more important for the nodule behavior than extra nodular factors. Conclusions: Our study demonstrates that the growth of benign thyroid nodules is inversely correlated to their size, benign nodules naturally growth slowly as time advances, and that a chronic treatment with L-T4 at a non-TSH-suppressive dose significantly reduces their growth.